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Inhibitory effects of intrathecal p38β antisense oligonucleotide on bone cancer pain in rats
Hang Dong1, Hong-Bing Xiang2, Da-Wei Ye3
1Department of Anesthesiology, Affiliated Hospital, Jianghan University Wuhan 430072, P. R. China ; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430030, P. R. China.
Objective:
To evaluate the effects of intrathecal administration p38β antisense oligonucleotide on the development of bone cancer pain rats.
Methods:
Forty female SD rats weighing 180~220 g were randomly divided into 4 groups (n = 10 each): Group A (control group): intra-tibial injection of 3 μl Hank's solution; group B (model group): intra-tibial injection of 3 μl MADB-106 mammary gland carcinoma cells of rats (4.8 × 10(3)/μl); group C (p38β-SODN 20 μg); group D (p38β-ASODN 20 μg). The model procedures in group C and D were same to those in the group B. From the 14th day after operation, p38β-SODN 20 μg and p38β-ASODN 20 μg were respectively intrathecally administrated in group C and D once daily for 6 days whereas normal saline was for group A and B. Mechanical withdrawal threshold and radiant heat threshold of rat hind paws were measured before operation and every other day until 22 d of post-operation. The lumbar 4-6 spinal cord was removed on the 22(nd) day. The expression of spinal p38β protein was determined by Western blot.
Results:
No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in control group. During the first 6 days after operation there were obvious differences in radiant heat stimulus between control group between the other groups (P < 0.05); During 14-22 days after operation, mechanical pain threshold and radiant heat threshold between p38β-SODN group and Model group were significantly changed compared with that in control group (P < 0.05). However, the differences were not remarkable between control group and p38β-ASODN group (P > 0.05). The expression of p38β protein in lumbar spinal cord was significantly higher between p38β-SODN group and Model group than that in control group (P < 0.05). There was no significant difference in p38β protein expression between p38β-ASODN group and control group (P > 0.05).
Conclusions:
Hyperalgesia induced by bone cancer can be inhibited by intrathecal administration of p38β antisense oligonucleotide, which is achieved by reducing expression of p38β protein.
